DNA vaccination is a technically simple way of inducing immune responses. However, success in small animals has not yet been reproduced in clinical trials. Several strategies are currently being pursued to increase efficacy of DNA vaccines.
Targeting of protein antigens to antigen-presenting cells (APC) can improve T- and B-cell responses. Recombinant immunoglobulin (Ig) molecules are well suited for this purpose. For example, short antigenic epitopes can replace loops between β-strands in the Ig constant domains while targeted antigen delivery is obtained by equipping the recombinant Ig with variable (V) regions specific for surface molecules on APC. However, such a strategy is unfit for larger antigens containing unidentified epitopes, moreover recombinant Ig molecules with short T cell epitopes fail to elicit antibodies against conformational epitopes. To overcome these limitations, targeted Ig-based homodimeric DNA vaccines (vaccibodies) have been generated that express infectious or tumor antigens with a size of at least 550 aa. with maintenance of conformational epitopes.
Chemokine (C—C motif) ligand 3 (CCL3) is a protein that in humans is encoded by the CCL3 gene. CCL3, also known as Macrophage inflammatory protein-1α (MIP-1α), is a cytokine belonging to the CC chemokine family that is involved in the acute inflammatory state in the recruitment and activation of polymorphonuclear leukocytes. While mouse CCL3 is a single copy gene encoding for a mature chemokine of 69 amino acids, the human homolog has been duplicated and mutated to generate two non-allelic variants, LD78α (CCL3) and LD78β (CCL3-L1), both showing a 74% homology with the mouse CCL3.
No DNA vaccine has so far been approved for human use due to lack of efficacy. Also there is no effective vaccine available for several infectious diseases. In particular, no therapeutic DNA cancer vaccine has been approved for human use.
WO 2004/076489 relates to recombinant human antibody-based molecule called Vaccibodies, which are able to trigger both a T cell- and B cell immune response.
US20070298051 relates to the use of MIP-1-alpha for enhancing the immune response to an immunogen in a mammal.
EP920522 relates to a polynucleotide vector vaccine comprising a cDNA target product that comprises a nucleotide sequence encoding a cytokine or chemokine.
Fredriksen A B et al. (Mol Ther 2006; 13:776-85) relates to DNA vaccines targeting tumor antigen to antigen-presenting cells.
Fredriksen A B and Bogen B (Blood 2007; 110:1797-805) relates to mouse chemokine-idiotype fusion DNA vaccines.